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The mitochondria-related gene risk mode revealed p66Shc as a prognostic mitochondria-related gene of glioblastoma.
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- معلومة اضافية
- المصدر:
Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
- بيانات النشر:
Original Publication: London : Nature Publishing Group, copyright 2011-
- الموضوع:
- نبذة مختصرة :
Numerous studies have highlighted the pivotal role of mitochondria-related genes (MRGs) in the initiation and progression of glioblastoma (GBM). However, the specific contributions of MRGs coding proteins to GBM pathology remain incompletely elucidated. The identification of prognostic MRGs in GBM holds promise for the development of personalized targeted therapies and the enhancement of patient prognosis. We combined differential expression with univariate Cox regression analysis to screen prognosis-associated MRGs in GBM. Based on the nine MRGs, the hazard ratio model was conducted using a multivariate Cox regression algorithm. SHC-related survival, pathway, and immune analyses in GBM cohorts were obtained from the Biomarker Exploration of the Solid Tumor database. The proliferation and migration of U87 cells were measured by CCK-8 and transwell assay. Apoptosis in U87 cells was evaluated using flow cytometry. Confocal microscopy was employed to measure mitochondrial reactive oxygen species (ROS) levels and morphology. The expression levels of SHC1 and other relevant proteins were examined via western blotting. We screened 15 prognosis-associated MRGs and constructed a 9 MRGs-based model. Validation of the model's risk score confirmed its efficacy in predicting the prognosis of patients with GBM. Furthermore, analysis revealed that SHC1, a constituent MRG of the prognostic model, was upregulated and implicated in the progression, migration, and immune infiltration of GBM. In vitro experiments elucidated that p66Shc, the longest isoform of SHC1, modulates mitochondrial ROS production and morphology, consequently promoting the proliferation and migration of U87 cells. The 9 MRGs-based prognostic model could predict the prognosis of GBM. SHC1 was upregulated and correlated with the prognosis of patients by involvement in immune infiltration. Furthermore, in vitro experiments demonstrated that p66Shc promotes U87 cell proliferation and migration by mediating mitochondrial ROS production. Thus, p66Shc may serve as a promising biomarker and therapeutic target for GBM.
(© 2024. The Author(s).)
- References:
Nat Neurosci. 2015 Apr;18(4):501-10. (PMID: 25730670)
Transl Oncol. 2021 Jan;14(1):100905. (PMID: 33069104)
Mol Cancer Ther. 2007 Jul;6(7):1909-19. (PMID: 17620423)
Oncogene. 2017 May 11;36(19):2724-2736. (PMID: 27941873)
Cancer Cell. 2017 Jul 10;32(1):42-56.e6. (PMID: 28697342)
Neuro Oncol. 2020 Oct 30;22(12 Suppl 2):iv1-iv96. (PMID: 33123732)
N Engl J Med. 2013 Oct 17;369(16):1561-3. (PMID: 24131182)
Trends Cell Biol. 2008 Apr;18(4):165-73. (PMID: 18296052)
Nat Rev Clin Oncol. 2018 Apr;15(4):234-248. (PMID: 29405201)
Cell Death Dis. 2016 Mar 03;7:e2123. (PMID: 26938295)
Mol Biol (Mosk). 2012 Jan-Feb;46(1):139-46. (PMID: 22642111)
Front Cell Dev Biol. 2021 Apr 13;9:617801. (PMID: 33928077)
Theranostics. 2019 May 26;9(12):3595-3607. (PMID: 31281500)
Drug Resist Updat. 2018 Nov;41:1-25. (PMID: 30471641)
J Biol Chem. 2013 Feb 8;288(6):4158-73. (PMID: 23250747)
Commun Biol. 2019 May 29;2:200. (PMID: 31149644)
N Engl J Med. 2005 Mar 10;352(10):987-96. (PMID: 15758009)
Genomics. 2021 Jan;113(1 Pt 2):767-777. (PMID: 33069830)
Mol Cell. 2016 Mar 3;61(5):667-676. (PMID: 26942671)
Nature. 2016 Jan 7;529(7584):110-4. (PMID: 26700815)
J Hematol Oncol. 2020 Oct 21;13(1):141. (PMID: 33087132)
BMC Cancer. 2013 Dec 31;13:617. (PMID: 24380367)
Curr Opin Cell Biol. 2016 Apr;39:43-52. (PMID: 26896558)
Endocrinology. 2005 May;146(5):2473-80. (PMID: 15705774)
Front Biosci (Landmark Ed). 2009 Jan 01;14(11):4015-34. (PMID: 19273331)
Nat Rev Mol Cell Biol. 2019 May;20(5):267-284. (PMID: 30626975)
Cell. 2009 Aug 21;138(4):628-44. (PMID: 19703392)
Nucleic Acids Res. 2019 Jul 2;47(W1):W556-W560. (PMID: 31114875)
J Clin Invest. 2010 Aug;120(8):2858-66. (PMID: 20664172)
Clin Cancer Res. 2000 Mar;6(3):1135-9. (PMID: 10741744)
Oncol Rep. 2013 Nov;30(5):2350-6. (PMID: 24026199)
Nature. 1999 Nov 18;402(6759):309-13. (PMID: 10580504)
Ageing Res Rev. 2020 Nov;63:101139. (PMID: 32795504)
Eur J Clin Invest. 2015 Jan;45 Suppl 1:25-31. (PMID: 25524583)
Front Immunol. 2016 Apr 26;7:156. (PMID: 27199982)
Autophagy. 2021 Mar;17(3):723-742. (PMID: 32186433)
Nat Rev Neurol. 2019 Jul;15(7):405-417. (PMID: 31227792)
Mol Carcinog. 2015 Aug;54(8):618-31. (PMID: 24395385)
Nature. 2012 Feb 15;483(7390):479-83. (PMID: 22343889)
Int J Oncol. 2005 Apr;26(4):905-11. (PMID: 15753984)
Nat Commun. 2017 Mar 09;8:14638. (PMID: 28276425)
J Biol Chem. 2004 Jan 16;279(3):2299-306. (PMID: 14573619)
Cancer Treat Rev. 2019 Nov;80:101896. (PMID: 31541850)
Breast Cancer Res. 2019 Jun 15;21(1):74. (PMID: 31202267)
Antioxid Redox Signal. 2014 Mar 1;20(7):1126-67. (PMID: 23991888)
Oncotarget. 2016 May 31;7(22):33440-50. (PMID: 26967052)
Nat Rev Cancer. 2012 Oct;12(10):685-98. (PMID: 23001348)
- Grant Information:
81801908 The National Nature Science Foundation of China; 2022JJ70163 Hunan Provincial Natural Science Committee Project
- Contributed Indexing:
Keywords: Glioblastoma; Immune infiltration; Mitochondria; ROS; p66Shc
- الرقم المعرف:
0 (SHC1 protein, human)
- الموضوع:
Date Created: 20240519 Date Completed: 20240519 Latest Revision: 20240604
- الموضوع:
20240605
- الرقم المعرف:
PMC11102912
- الرقم المعرف:
10.1038/s41598-024-62083-2
- الرقم المعرف:
38763954
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